Glucosamine enhances heat shock protein 70 expression in vitro and in vivo following injury

Introduction

Enhanced activity of the O-glycosylation pathway (O-glcNAc) has been shown to enhance increase heat shock protein (HSP70) expression. Glucosamine (GA) is a vital intermediate in this pathway.

Methods

Mouse fibroblast (MEF) cells underwent heat stress (HS) at 43°C for 45 minutes. GA doses from 1.25 to 20 mM were given immediately prior to HS. Cell survival was assessed via MTS assay. GA's effect on HSP70 expression in vivo was assessed using a mouse model of cecal ligation and puncture (CLP). Mice were given 0.26 g/kg GA i.v. 1 hour post CLP.

Results

In MEF cells, 10 mM GA led to a 164% increase in HSP70 expression over control 4 hours post HS (P < 0.05 vs control). Further, GA treatment led to an increase in cell survival post HS injury at all doses tested (P < 0.01 vs control). Following CLP-induced sepsis, a single dose of GA led to an increase in lung and heart HSP70 at 1 and 2 hours post CLP vs saline control (SC). This effect was lost at 6 and 24 hours (see Figure 1, *P < 0.05 versus SC at each timepoint). Similarly, GA led to an increase in HSP70 in colon tissue as well, with the effect lasting to 6 hours (*P < 0.05 versus SC). The effect in colon was lost by 24 hours.

Figure 1

Lung heat shock protein (HSP70) expression in glucosamine vs saline following cecal ligation and puncture.

Conclusion

To our knowledge, this is the first report that shows GA treatment can increase HSP70 expression both in vivo and in vitro. Previous data have demonstrated beneficial effects of GA treatment following ischemia/reperfusion injury and hemorrhagic shock early after injury. GA's effect on HSP70 expression in multiple tissues may help to explain these effects. Further, GA's effect on HSP70 expression may be an important factor involved in GA's benefits in arthritis and joint disease.